Anticipating the future: automatic prediction failures in schizophrenia

Abstract

People with schizophrenia often misperceive sensations and misinterpret experiences, perhaps contributing to psychotic symptoms. These misperceptions and misinterpretations might result from an inability to make valid predictions about expected sensations and experiences. Healthy normal people take advantage of neural mechanisms that allow them to make predictions unconsciously, facilitating processing of expected sensations and distinguishing the expected from the unexpected. In this paper, we focus on two types of automatic, unconscious mechanisms that allow us to predict our perceptions. The first involves predictions made via innate mechanisms basic to all species in the animal kingdom - the efference copy and corollary discharge mechanisms. They accompany our voluntary movements and allow us to suppress sensations resulting from our actions. We study this during talking, and show that auditory cortical response to the speech sounds during talking is reduced compared to when they are played back. This suppression is reduced in schizophrenia, suggesting a failure to predict the sensations resulting from talking. The second mechanism involves implicitly learning what to expect from the current context of events. We study this by observing the brain's response to an unexpected repetition of an event, when a change would have been predicted. That patients have a reduced response suggests they failed to predict that it was time for a change. Both types of predictions should happen automatically and effortlessly, allowing for economic processing of expected events and orientation to unexpected ones. These prediction failures characterize the diagnosis of schizophrenia rather than reflecting specific symptoms.

Figure 1

(Left) We show a cartoon profile of a healthy control subject talking (saying “ah”) and listening to a playback of “ah”. Above the heads, we show ERPs recorded from the vertex (Cz) elicited by the onset of the speech sound (dotted vertical line) during talking (red lines) and listening (blue lines). During talking, N1 to the speech sound is suppressed relative to N1 to the same sound during listening. Amplitude (microvolts) is on the y-axis and time (milliseconds) is on the x-axis. Vertex negativity is plotted down. The N1 of the ERP is generated in auditory cortex (colored orange during Talk, and blue during Listen). Intensity of the color in the auditory cortex denotes the strength of the response to the speech sound. The intention to say “ah” is indicated as an orange “thought bubble” over Broca's area. The orange curved arrow pointing from Broca's area to auditory cortex indicates the transmission of the efference copy of the motor plan, which produces a corollary discharge (orange burst) of the expected sensation in auditory cortex. When the expected sensation (corollary discharge) matches the actual sensation (sensory reafference) in auditory cortex (green burst), perception is suppressed. (Right). The same is shown for schizophrenia patients, with a relative failure of the efference copy and corollary discharge being shown as faded orange. The slightly more intense orange color in auditory cortex during talking indicates relatively less suppression of the auditory cortical response to the spoken sound. The slightly less intense blue color during listening indicates an overall tendency of patients to generate a smaller N1 to sounds during passive listening. (Permission from Schizophrenia Bulletin to reproduce elements of this figure is pending.)

Figure 2

ERPs from Fz, FCz, Cz, CPz, and Pz, locked to speech sound onset (0ms, dotted vertical line) are shown for each of the three experiments: Talking, Expectancy, and Agency, for the healthy controls. ERPs elicited during the two conditions for each experiment are overlaid. Amplitude (microvolts) is on the y-axis and time (milliseconds) is on the x-axis. Negativity is plotted down. (Permission from Psychophysiology to reproduce elements of this figure is pending.)

Figure 3a

Grand average ERPs from Cz following Standard #3, regardless of whether the next stimulus was Standard #4, a Target or a Novel. Data from controls and patients are overlaid. This analysis allows the visualization and quantification of the Stimulus Preceding Negativity (SPN) or the contingent negative variation (CNV). Here and throughout Figure 3, amplitude (microvolts) is on the y-axis and time (milliseconds) is on the x-axis. Dotted lines indicate onset of Standard #3 at 0ms, 300ms, and onset of the next stimulus at 1250ms. Positivity relative to the reference electrodes is plotted up.

Figure 3b

Grand average ERPs for 4 consecutive standards following a deviant stimulus in healthy controls (left) and patients with schizophrenia (right) for frontal, central, and parietal midline sites, Fz, Cz and Pz. ERPs are time-locked to the onset of each of the four consecutive standards, Standard #1, #2, #3, and #4, baseline corrected to the preceding 100ms. Vertical lines are at 0ms (stimulus onset), 100ms and 300ms. Note that only Standard #4 evokes a P3a.

Figure 3c

Grand average ERPs from vertex (Cz) resulting from the subtraction of the ERP to Standard #1 from Standard #4 (S4–S1), overlaid for controls and patients, filtered with a 1Hz filter to remove the slow neural activity seen in Figure 3a. This subtraction allows the visualization and quantification of the N2b/MMN component elicited by Standard #4. Amplitude (microvolts) is on the y-axis and time (milliseconds) is on the x-axis. Negativity is plotted down. Dotted line indicates onset of Standard #4. (Permission from the International Journal of Psychophysiology to reproduce elements of this figure is pending.)